Summary
Hip fracture is one of the most severe consequences of osteoporosis affecting aged women. However, abnormalities of bone turnover responsible for bone loss in this condition have not been clearly defined. To further evaluate the bone metabolic status of women sustaining hip fracture, we have prospectively measured serum osteocalcin as a marker of bone formation and urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (D-pyr) cross-links as markers of bone collagen degradation in 174 independently living women (80 ± 8 years) within a few hours after a hip fracture. Comparison was made with 77 age-matched controls (80 ± 5 years) and 17 premenopausal women (39 ± 3 years). In addition 15 of the patients were followed with daily measurements during the first postoperative week. At the time of admission osteocalcin was 20% lower in the fractured women compared to the elderly controls (7.6 ± 3.8 vs. 9.5 ± 4.5 nglml,P = 0.001). Pyr and D-pyr were 36% and 40% higher, respectively (P = 0.0001), than in elderly controls and 85% and 76% higher than in premenopausal controls (P = 0.0001). Serum osteocalcin did not correlate with the cortisol level measured at the same time (r = 0.03, ns), nor with serum albumin and creatinine. Serum osteocalcin remained unchanged within 18 hours after fracture, whereafter it progressively decreased until the third postoperative day. No correlation was noted between the excretion of pyridinoline cross-links and the time elapsed from fracture.
These data suggest that the abnormal levels of osteocalcin and pyridinolines are unrelated to traumatically induced acute changes, but reflect abnormalities of bone turnover existing prior to the fracture. Thus, hip-fracture patients have biochemical evidence of decreased bone formation and increased bone resorption when compared to age-matched controls. We suggest that these abnormalities may play a role in the decrease of the bone mass and the consequently increased bone fragility that characterize the osteoporotic hip fracture in the elderly.
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References
Obrant KJ, Bengnér U, Johnell O, Nilsson BE, Sernbo I (1989) Increasing age-adjusted risk of fragility fractures: a sign of increasing osteoporosis in successive generations? Calcif Tissue Int 44:157–167
Riggs BL, Wahner HW, Seeman E, Offord KP, Dunn WL (1982) Changes in bone mineral density of the proximal femur and spine with aging. J Clin Invest 70:716–723
Duboeuf F, Braillon P, Chapuy MC, et al (1991) Bone mineral density of the hip measured with Dual-Energy X-ray absorptiometry in normal elderly women and in patients with hip fracture. Osteoporosis Int 1:242–249
Lips P, Jongen MJM, van Ginkel FC, et al (1982) Histomorphometric profile and vitamin D status in patients with femoral neck fracture. Metabol Bone Dis Rel Res 4:85–93
Uitewaal PJM, Lips P, Netelenbos JC (1987) An analysis of bone structure in patients with hip fracture. Bone Miner 3:63–73
Aaron JE, Stasiak L, Gallagher JC, et al (1974) Frequency of osteomalacia and osteoporosis in fractures of the proximal femur. Lancet (February 16):229–233
Lips P, Obrant KJ (1991) The pathogenesis and treatment of hip fractures. Osteoporosis Int 1:218–231
Price PA, Otsuka AS, Poster JW, Kristaponis J, Roman N (1976) Primary structure of the gamma-carboxyglutamic acidcontaining protein from bovine bone. Proc Natl Acad Sci USA 73:1447
Hauschka PV, Lian JB, Gallop PM (1975) Direct identification of the calciumbinding amino acid, gamma-carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci USA 72(10):3925–3929
Delmas P (1988) Biochemical markers of bone turnover in osteoporosis. In: Riggs LB, Melton LJ (eds) Osteoporosis: etiology, diagnosis and management. New York, Raven Press, pp 297–316
Delmas P (1990) Biochemical markers of bone turnover for the clinical assessment of metabolic bone disease. Endocrinol Metab Clin North Am 19(1):1–18
Delmas P, Stenner D, Wahner HW, Mann KG, Riggs BL (1983) Increase in serum bone gamma-carboxyglutamic acid protein with aging in women: implications for the mechanism of agerelated bone loss. J Clin Invest 71(May):1316–1321
Epstein SRM, Bryce G, Poser J, Johnston CCJ, Hui S (1984) Differences in serum bone Gla-protein with age and sex. Lancet (Feb 11):307–310
Johansen JS, Riis BJ, Delmas PD, Christiansen C (1988) Plasma BGP: an indicator of spontaneous bone loss and of the effect of oestrogen treatment in postmenopausal women. Eur J Clin Invest 8:191–195
Kelly PJ, Pocock NA, Sambrook PN, Eisman JA (1989) Age and menopause-related changes in indices of bone turnover. J Clin Endocrinol Metab 69(6):1160–1165
Slovik DM, Gundberg CM, Neer RM, Lian JB (1984) Clinical evaluation of bone turnover by serum osteocalcin measurements in a hospital setting. J Clin Endocrinol Metab 59(2):228–230
Lips P, Bouillon R, Jongen MJM, van Ginkel FC, van der Vijgh WJF, Netelenbos JC (1985) The effect of trauma on serum concentrations of vitamin D metabolites in patients with hip fracture. Bone 6:63–67
Cooper C, Mclaren M, Wood PJ, Coulton L, Kanis JA (1989) Indices of calcium metabolism in women with hip fracture. Bone Miner 5:193–200
Eyre DR, Koob TJ, Van Ness KP (1984) Quantitation of hydroxypyridinium crosslinks in collagen by high-performance liquid chromatography. Anal Biochem 137:380–388
Eyre DR (1987) Collagen cross-linking amino-acids. In: Cunningham LW (ed) Methods in enzymology. New York, Academic Press, 144:115–139
Fujimoto D (1982) Aging and cross linking in human aorta. Biochem Biophys Res Commun 109:1264–1269
Black D, Duncan A, Robins SP (1988) Quantitative analysis of the pyridinium crosslinks of collagen in urine using ion-paired reversed-phase high-performance liquid chromatography. Anal Biochem 169:197–203
Seibel MJ, Duncan A, Robins SP (1989) Urinary hydroxypyridinium crosslinks provide indices of cartilage and bone involvement in arthritic diseases. J Rheumatol 16(7):964–970
Robins SP, Stewart P, Astbury C, Bird HA (1986) Measurements of the cross linking compound, pyridinoline, in urine as an index of collagen degradation in joint disease. Ann Rheum Dis 45:969–973
Uebelhart PJM, Gineyts E, Chapuy M-C, Delmas PD (1990) Urinary excretion of pyridinium crosslinks: a new marker of bone resorption in metabolic bone disease. J Bone Miner 8:87–96
Delmas P, Sclemmer A, Gineyts E, Riis B, Christiansen C (1991) Urinary excretion of pyridinoline crosslinks correlates with bone turnover measured on iliac crest biopsy in patients with vertebral osteoporosis. J Bone Min Res 6(6):639–644
Merle B, Delmas PD (1990) Normal carboxylation of circulating osteocalcin (bone Gla-protein) in Paget's disease of bone. Bone Miner 11:237–245
Thorell J, Larsson SM (1978) Radioimmunoassay and related techniques. In: Kortisol S (ed). CV Mosby, St Louis, pp 131–136
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41
Benhamou CL, Popelier M, Gauvain JB, et al (1989) Métabolisme phospho-calcique et hormones calciotropes dans la fracture du col du fémur après 70 ans. Revue du Rhumatisme 56(12):835–841
Lamberg-Allardt C, von Knorring J, Slätis P, Holmström T (1989) Vitamin D status and concentration of serum vitamin D metabolites and osteocalcin in elderly patients with femoral neck fracture—a follow-up study. Eur J Clin Nutr 43:355–361
Thompson SP, White DA, Hosking DJ, Wilton TJ, Pawley E (1989) Changes in osteocalcin after femoral neck fracture. Ann Clin Biochem 26:487–491
Obrant KJ, Merle B, Bejui J, Delmas PD (1990) Serum bone Gla-protein after fracture. Clin Orthop Rel Res 258:300–303
Nilsson BE, Westlin NE (1972) The plasma concentration of alkaline phosphatase, phosphorus and calcium following femoral neck fracture. Acta Orthop Scand 43:504–510
Sharland DE, Overstall PW (1978) Alkaline phosphatase: changes in serum levels after a fracture. Brit Med J 11:620
Hosking DJ (1978) Changes in serum alkaline phosphatase after femoral fractures. J Bone Joint Surg (Br) 60-B(Febr):61–65
Kaalund Jensen H, Blichert-Toft M (1971) Serum corticotrophin, plasma cortisol and urinary excretion of 17-ketogenic steroids in the elderly (age group: 66–94 years). Acta Endocrinol 66:25–34
Oyama T, Taniguchi K, Takazawa T, Matsuki A, Kudo M (1980) Effect of anaesthesia and surgery on endocrine function in elderly patients. Can Anaesth Soc J 27(6):556–559
Adams HA, Wolf C, Michaelis G, Hempelmann G (1990) Postoperativer Verlauf und endokrine Stress-Reaktion geriatrischer Patienten mit hüftnahen Frakturen. Anästh Intensivther Notfallmed 25:262–270
Brwen DJ, Richardson DJ (1974) Adrenocortical response to major surgery and anaesthesia in elderly patients. Br J Anaesthesia 46:873
Jennings BH, Andersson KE, Johansson SA (1991) Assessment of systemic effects of inhaled glucocorticosteroids: comparison of the effects of inhaled budesonide and oral prednisolone on adrenal function and markers of bone turnover. Eur J Clin Pharmacol 40(1):77–82
Peretz A, Praet JP, Bosson D, Rozenberg S, Bourdoux P (1989) Serum osteocalcin in the assessment of corticosteroid induced osteoporosis. Effect of long and short term corticosteroid treatment. J Rheumatol 16(3):363–367
Fortune CL, Farrugia W, Tresham J, Scoggins BA, Wark JD (1989) Hormonal regulation of osteocalcin plasma production and clearance in sheep. Endocrinology 124(6):2785–2790
Delmas P, Wahner HW, Mann KG, Riggs BL (1983) Assessment of bone turnover in postmenopausal osteoporosis by measurement of serum bone Gla-protein. J Lab Clin Med 102(4):470–476
Brown JP, Malaval L, Chapuy MC, Delmas PD, Eduoard C, Meunier PJ (1984) Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet May 19:1091–1093
Francis RM, Peacock M, Barkworth SA (1984) Renal impairment and its effects on calcium metabolism in elderly women. Age Ageing 13:14–20
Hadji-Aïssa A, Dumarest C, Maire P, Pozet N (1990) Renal function in the elderly. Nephron 54:364–365
Lips P, van Ginkel FC, Netelenbos JC, Wiersinga A, van der Vijgh WIT (1990) Lower mobility and markers of bone resorption in the elderly. Bone Miner 9:49–57
Sernbo I, Johnell O (1986) Health and social status in patients with hip fractures and controls. Age Ageing 15:285–291
Gärdsell P, Johnell O, Nilsson BE (1991) The impact of menopausal age on future fragility fracture risk. J Bone Min Res 6(5):429–433
Hordon LD, Peacock M (1990) Osteomalacia and osteoporosis in femoral neck fracture. Bone Miner 11:247–259
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Åkesson, K., Vergnaud, P., Gineyts, E. et al. Impairment of bone turnover in elderly women with hip fracture. Calcif Tissue Int 53, 162–169 (1993). https://doi.org/10.1007/BF01321832
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DOI: https://doi.org/10.1007/BF01321832